title: The potential of the human immune system to develop broadly neutralizing HIV-1 antibodies: implications for vaccine development.
abstract: OBJECTIVE
  Developing an effective HIV-1 vaccine that elicits broadly neutralizing HIV-1 human antibodies (bnAbs) remains a challenging goal. Extensive studies on HIV-1 have revealed various strategies employed by the virus to escape host immune surveillance. Here, we investigated the human antibody gene repertoires of uninfected and HIV-1-infected individuals at genomic DNA (gDNA) and cDNA levels by deep sequencing followed by high-throughput sequence analysis to determine the frequencies of putative germline antibody genes of known HIV-1 monoclonal bnAbs (bnmAbs).
  
  
  METHODS
  Combinatorial gDNA and cDNA antibody libraries were constructed using the gDNAs and mRNAs isolated from uninfected and HIV-1-infected human peripheral blood mononuclear cells (PBMCs). All libraries were deep sequenced and sequences analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index.action). The frequencies of putative germline antibodies of known bnmAbs in the gDNA and cDNA libraries were determined.
  
  
  CONCLUSIONS
  The human gDNA antibody libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries, indicating that the human gDNA antibody gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnAbs. The frequencies of the heavy and kappa and lambda light chain variable regions with identical V(D)J recombinations to known HIV-1 bnmAbs were extremely low in human antibody gene repertoires. However, we found relatively high frequencies of the heavy and kappa and lambda light chain variable regions that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. B-cells bearing B-cell receptors of such heavy and kappa and lambda light chain variable regions may be stimulated to induce HIV-1 bnAbs.
authors.affiliation: aAIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong bInstitutes of Biomedical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai cDivision of Research on Virology and Immunology, National Center for AIDS/STD Control and Prevention, China CDC, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tingting
authors.initials: T
authors.lastname: Yuan
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.forename: Mei-Yun
authors.initials: MY
authors.lastname: Zhang
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000235:genetics* / Q000276:immunology*; D015723:Gene Library; D015483:HIV Antibodies / Q000235:genetics* / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D064368:Healthy Volunteers; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007963:Leukocytes, Mononuclear
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies